Exposure Biomarkers of Polyfluoroalkyl Compounds in Persons Living in the Ohio River Valley Polyfluoroalkyl compounds (PFCs) such as perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) have been detected in humans and wildlife, and are associated with adverse health effects in laboratory animals and humans. Research in animals has noted immunotoxicity in several species, which may be secondary to the activity of PFOA as an agonist to the peroxisome proliferators activated receptor-1 (PRAR-1), although no clinical evidence of immune system perturbation has been noted in humans. In studies of PFC environmental biomarkers in 6-8 year-old girls from Greater Cincinnati (N=60), we found that 38/42 girls living in one school district of Northern Kentucky (NKY) had serum PFOA concentrations that were above the NHANES 2003- 2004 95th percentile value for children 12-19 years (8.6 ng/ml), with a geometric mean of 16.8 ng/ml. The analysis of their residential history data suggested that the exposure was present throughout NKY and not limited to one school district, and that the time of primary exposure was prior to 2002. Length of residence in NKY and being breast fed were significant predictors of serum PFOA. In the proposed study, we will (Aims 1 and 2) sample serum from 510 persons throughout the Ohio River Valley, using the river as a drinking water source, and in areas served by two different water treatment systems, to determine the prevalence of serum PFOA concentration above the NHANES 95th percentile, (Aim 3) use information about the geographical distribution and residential history of those with elevated concentrations to determine the existence and strength of modifiers of serum PFOA concentrations, in those of different ages, gender, pregnancy status, and history of being breast fed, and (Aim 4) determine if those with the highest serum PFOA or PFOS concentrations exhibit evidence of an inflammatory response, using molecular markers of interleukins and C-reactive protein, or if serum PFOA or PFOS concentration is related to body mass index.